Apparatus And Method For Coating And Drying Multiple Stents

ABSTRACT

A coating and drying apparatus for the application of a coating substance to a stent and drying the stent is provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. application Ser. No. 10/315,457,filed on Dec. 9, 2002.

TECHNICAL FIELD

This invention relates to an apparatus used in the process of coatingand drying stents, and more particularly provides an apparatus forcoating and drying a plurality of stents.

BACKGROUND

Blood vessel occlusions are commonly treated by mechanically enhancingblood flow in the affected vessels, such as by employing a stent. Stentsact as scaffolding, functioning to physically hold open and, if desired,to expand the wall of affected vessels. Typically stents are capable ofbeing compressed, so that they can be inserted through small lumens viacatheters, and then expanded to a larger diameter once they are at thedesired location. Examples in the patent literature disclosing stentsinclude U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No.4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued toWiktor.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy can beachieved by medicating the stents. Medicated stents provide for thelocal administration of a therapeutic substance at the diseased site.Local delivery of a therapeutic substance is a preferred method oftreatment because the substance is concentrated at a specific site andthus smaller total levels of medication can be administered incomparison to systemic dosages that often produce adverse or even toxicside effects for the patient.

One method of medicating a stent involves the use of a polymeric carriercoated onto the surface of the stent. A composition including a solvent,a polymer dissolved in the solvent, and a therapeutic substancedispersed in the blend is applied to the stent by spraying thecomposition onto the stent. The solvent is allowed to evaporate, leavingon the stent surfaces a coating of the polymer and the therapeuticsubstance impregnated in the polymer. In order to quicken the process,the stents may be baked so that the solvent evaporates quickly.

Shortcomings of the above-described method of medicating a stent is thepotential for shot to shot variation of the coating weight and the needfor baking or otherwise drying each stent after the coating application.These two shortcomings limit production throughput. Specifically, aftereach coating process (e.g., primer, drug coat, topcoat), the stent mustbe weighed to calculate the amount of drug and polymer deposited ontothe stent. In addition, up to two hours bake time can be required toevaporate the solvent from the stent.

Accordingly, a new apparatus for spraying coating is needed to increaseproduction throughput.

SUMMARY

In accordance with one embodiment, a stent coating and drying apparatusis provided, comprising a chamber for receiving a cartridge, the chamberincluding a drying section and a spray coating section. The cartridgecan have a plurality of stent mandrels for supporting the stents. Thecartridge is capable of moving a stent supported on a stent mandrel fromthe spray coating section to the drying section or from the dryingsection to the spray coating section of the chamber. A spray applicatoris used for spraying the coating substance onto the stent when the stentis positioned in the spray coating section of the chamber. In oneembodiment, the chamber is in communication with a heated gas supply forsupplying heated gas to the drying section of the chamber. The stentmandrels can be evenly distributed and extending out from thecircumference of the cartridge. The spray coating section is at leastpartially sectioned off from the drying section of the chamber.Additionally, the drying section can include a vent that discharges theheated gas that is applied into the chamber.

In accordance with another embodiment, a cartridge is provided,comprising a core and a plurality of stent mandrels extending outwardsfrom a circumference of the core, each stent mandrel capable ofsupporting a stent. A first clutch can be coupled to the core andcapable of being removeably coupled to a first shaft such that rotationof the first shaft enables rotation of the core. A second clutch can becoupled to the plurality of stent mandrels and capable of beingremoveably coupled to a second shaft such that rotation of the secondshaft enables rotation of the stent mandrels.

In accordance with another embodiment, a system for forming a coating ona stent is provided comprising a hub for holding at least one cartridge,the cartridge capable of having a plurality of stents supported thereon;a chamber capable of receiving the cartridge for the application of acoating substance to the stents; an arm capable of moving the cartridgebetween the hub and the chamber; and a spray applicator capable ofapplying a coating composition to the stent.

In accordance with another embodiment, a method for forming a coating ona stent is provided, comprising: placing a cartridge within a chamber,the chamber including a drying section and a spray coating section, thecartridge having a plurality of stent mandrels each supporting a stent;positioning a stent in the spray coating section of the chamber; andapplying a coating composition to the stent in the spray coating sectionof the chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments of the present invention aredescribed with reference to the following figures, wherein likereference numerals refer to like parts throughout the various viewsunless otherwise specified.

FIG. 1 is a diagram illustrating a multiple stent coater/dryerapparatus;

FIG. 2 is a diagram illustrating a cross section of the multiple stentcoater/dryer apparatus;

FIG. 3 is a diagram illustrating a cross section of a portion thecoating/drying chamber;

FIG. 4 is a block diagram illustrating controlling electronics inaccordance with one embodiment of the present invention;

FIG. 5 is a diagram illustrating a profile of the cartridge;

FIG. 6 is a diagram illustrating the coating/drying chamber holding acartridge; and

FIG. 7 is a diagram illustrating the coating/drying chamber holding acartridge with a coating applicator.

DETAILED DESCRIPTION

The following description is provided to enable any person havingordinary skill in the art to make and use the invention, and is providedin the context of a particular application and its requirements. Variousmodifications to the embodiments will be readily apparent to thoseskilled in the art, and the generic principles defined herein may beapplied to other embodiments and applications without departing from thespirit and scope of the invention. Thus, the present invention is notintended to be limited to the embodiments shown, but is to be accordedthe widest scope consistent with the principles, features and teachingsdisclosed herein.

FIG. 1 is a diagram illustrating a multiple stent coater/dryer apparatus100. The multiple stent coater/dryer apparatus 100 enables the coatingand simultaneous drying of stents, thereby increasing throughput. Barestents are manually loaded onto a circular cartridge 500 (FIG. 5), whichcan hold twelve to eighteen stents in one embodiment of the invention.The cartridge 500 is then manually placed in a loading bay on acircular-shaped hub 105. An engine 110 rotates the hub 105 in a counterclockwise direction such that a handle 510 of the cartridge 500 passesthrough a gate 115, thereby indicating that the cartridge 500 isoriented correctly so that an arm 120 can pick up the cartridge 500.

After the cartridge 500 passes through the gate 115, the arm 120 picksup the cartridge 500 via the handle 510 and carries the cartridge 500 toa secondary chamber for coating and drying stents on the cartridge 500.The arm 120 then securely places the cartridge 500 into a base 125 of acoating/drying chamber 600 (FIG. 6). After placement, a lever 135 lowersa cap 140 onto the base 125 so as to form the coating/drying chamber600. The lever 135 also lowers an anvil 145 onto the handle 510 of thecartridge 500. As will be discussed further below, the cartridge 500rotates within the coating/drying chamber 600 such that while one stentis being coated by a coating applicator 740, other stents mounted on thecartridge 500 are dried (and/or preheated for coating). In an embodimentof the invention, a dryer 130 is in communication with thecoating/drying chamber 600 to supply heated air to dry the stentsmounted on the cartridge 500.

FIG. 2 is a diagram illustrating a cross section of the multiple stentcoater/dryer apparatus 100. The apparatus includes a shaft 200 coupledto the engine 110 and the hub 105 that is used to rotate the hub 105.Engines 210 and 220 rotate an inner shaft 320 and an outer shaft 330,respectively. As will be discussed further below, the outer shaft 330rotates the cartridge 500 and the inner shaft 320 rotates stent mandrels520 (FIG. 5) of the cartridge 500.

FIG. 3 is a diagram illustrating a cross section of a portion thecoating/drying chamber 600. The chamber 600 includes the base 125 andthe cap 140. The base 125 includes an air inlet 300 for receiving heatedair and an air outlet 310 for exhausting heated air, thereby enablingthe circulation of heated air within the chamber 600. The outer shaft330 is coupled to the cartridge 500 via an outer clutch 550 (FIG. 5) andthe components engage by the pressure applied by the anvil 145.Accordingly, lifting of the lever 135 will enable the decoupling of thecartridge 500 from the outer shaft 330. Coupled to the outer shaft 330is gear 340, which is interlocked with the outer shaft 330 such thatrotation of the gear 340 causes outer shaft 330 to rotate. The innershaft 320 is also coupled to the cartridge 500 via an inner clutch 540(FIG. 5) via pressure applied by the anvil 145. Rotation of the innershaft 320 causes the mandrels 520 to rotate during spraying and drying,as will be discussed further below.

FIG. 4 is a block diagram illustrating controlling electronics 400 inaccordance with an embodiment of the present invention. In an embodimentof the invention, the controlling electronics 400 controls substantiallyall aspects of the multiple stent coater/dryer apparatus 100.Specifically, the controlling electronics 400 controls rotation of thehub 105; linear movement of the arm 120; vertical movement of the lever135; temperature and pressure of air produced by the dryer 130; rotationof the outer shaft 330; rotation of the inner shaft 320; and the coatingapplicator 740.

The controlling electronics 400 includes a central processing unit (CPU)405; working memory 410; persistent memory 420; input/output (I/O)interface 430; display 440 and input device 450, all communicativelycoupled to each other via system bus 460. CPU 405 may include an IntelPentium® microprocessor, a Motorola PowerPC® microprocessor, or anyother processor capable to execute software to control the multiplestent coater/dryer apparatus 100 that is stored in persistent memory420. Working memory 410 may include random access memory (RAM) or anyother type of read/write memory devices or combination of memorydevices. Persistent memory 420 may include a hard drive, read onlymemory (ROM) or any other type of memory device or combination of memorydevices that can retain data after controlling electronics 400 is shutoff. I/O interface 430 is communicatively coupled, via wired or wirelesstechniques, to the components of the multiple stent coater/dryerapparatus 100 that the controlling electronics 400 controls. Display 440may include a liquid crystal display or other display device. Inputdevice 450 may include a keyboard, mouse, or other device for inputtingdata, or a combination of devices for inputting data.

One skilled in the art will recognize that the controlling electronics400 may also include additional devices, such as network connections,additional memory, additional processors, LANs, input/output lines fortransferring information across a hardware channel, the Internet or anintranet, etc. One skilled in the art will also recognize that theprograms and data may be received by and stored in the system inalternative ways.

FIG. 5 illustrates a profile of the cartridge 500. The cartridgeincludes a plurality of stent mandrels 520 and associated knobs 530, thehandle 510, the inner clutch 540, and the outer clutch 550. The arm 120picks up the cartridge 500 via the handle 510 and moves it between thehub 105 and the base 125. Specifically, before coating and drying, thearm 120 moves the cartridge 500 via the handle 510 from the hub 105 tothe base 125. After coating and drying, the arm 120 removes thecartridge 500 from the base 125 and returns it to the hub 105. The stentmandrels 520 hold stents during coating and drying processes. In anembodiment, the stent mandrels 520 includes up to eighteen stentmandrels 520 distributed around the periphery of the cartridge 500. Theinner clutch 540 is coupled to the stent mandrels 520 such that rotationof the inner clutch 540 causes rotation of the stent mandrels 520. Thisallows rotation of the stents along the longitudinal axis of the stents.Rotational forces applied to the outer clutch 550 causes rotation of theentire cartridge 500.

FIG. 6 is a diagram illustrating the coating/drying chamber 600 holdingthe cartridge 500. The drying chamber 600 comprises the base 125 and thecap 140 and holds the cartridge 500, which rotates counter clockwisewithin the drying chamber 600 in an embodiment. The base 125 and cap 140both have open cylinder shapes that when combined form a closedcylindrical shape.

The coating/drying chamber 600 also includes a spray chamber 670, whichexposes a single stent mandrel 520 to spray coating from the coatingapplicator 740 (FIG. 7). The spray chamber 670 is formed by an opensection of the cap 140 with gates 640 a and 640 b (also referred to asflaps) sectioning off the remainder of the spray chamber 670 from thecoating/drying chamber 600. The gates 640 a and 640 b are coupled to thetop of cap 140 with hinges such that pressure applied to the gates 640 aand 640 b (e.g., via knobs 530) cause them to rotate upwards from avertical position to a horizontal position thereby enabling the stentmandrels 520 to pass through the gates 640 a and 640 b.

The remainder of the coating/drying chamber 600 forms a drying chamberwithin which circulates heated air to preheat stents before coating andto dry stents after coating. A tubing 660 couples dryer 130 to thedrying chamber section of the coating/drying chamber 600 via inlet 300for receiving heated air. The heated air rotates through thecoating/drying chamber 600 in a counter clockwise direction and exitsvia outlet 310, which is coupled to a tubing 650. The tubing 650 can becoupled to a filtering device (not shown) or other device for collectingand/or filtering the heated air, which may contain chemicals (e.g.,solvents and drugs) from the coating process.

During rotation of the cartridge 500 within the coating/drying chamber600, the knobs 530, which are metallic, push open the gate 640 a so thatthe a stent mandrel 520 can enter the spray chamber 670. In addition,the knobs 530 push open gate 640 b so that a recently coated stent on astent mandrel 520 can enter the drying chamber. A sensor (not shown)comprising a metal detector or other device detects and determines theposition of at least one of the knobs 530 and provides feedback tocontrol electronics 400, which then controls rotation of the cartridge500 such that a stent mandrel 520 is positioned correctly in the spraychamber 670.

Adjacent to the spray chamber 670 are circular vents 620 a and 620 blocated in the rim of the cap 140. Additionally, rectangular vents 610 aand 610 b are located on the top of the cap 140 adjacent to the spraychamber 670. The base 125 also includes two circular vents 630 a and 630b located beneath vents 620 a and 620 b respectively. These vents enableexcess heated air to vent from the drying section of the coating/dryingchamber 600 without interfering with a coating process.

The coating process, as will be described in further detail inconjunction with FIG. 7, sprays a coating substance onto stents mountedon the stent mandrels 520. The coating substance can include a solventand a polymer dissolved in the solvent and optionally a therapeuticsubstance or a drug added thereto. Representative examples of polymersthat can be used to coat a stent include ethylene vinyl alcoholcopolymer (commonly known by the generic name EVOH or by the trade nameEVAL), poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone;poly(lactide-co-glycolide); poly(hydroxybutyrate);poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;polyainhydride; poly(glycolic acid); poly(D,L-lactic acid);poly(glycolic acid-co-trimethylene carbonate); polyphosphoester;polyphosphoester urethane; poly(amino acids); cyanoacrylates;poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether esters)(e.g. PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules,such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid; polyurethanes; silicones; polyesters; polyolefins; polyisobutyleneand ethylene-alphaolefin copolymers; acrylic polymers and copolymers;vinyl halide polymers and copolymers, such as polyvinyl chloride;polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidenehalides, such as polyvinylidene fluoride and polyvinylidene chloride;polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such aspolystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers ofvinyl monomers with each other and olefins, such as ethylene-methylmethacrylate copolymers, acrylonitrilestyrene copolymers, ABS resins,and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 andpolycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;polyimides; polyethers; epoxy resins; polyurethanes; rayon;rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate;cellulose acetate butyrate; cellophane; cellulose nitrate; cellulosepropionate; cellulose ethers; and carboxymethyl cellulose.

“Solvent” is defined as a liquid substance or composition that iscompatible with the polymer and is capable of dissolving the polymer atthe concentration desired in the composition. Examples of solventsinclude, but are not limited to, dimethylsulfoxide, chloroform, acetone,water (buffered saline), xylene, methanol, ethanol, 1-propanol,tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide,cyclohexanone, ethyl acetate, methylethylketone, propylene glycolmonomethylether, isopropanol, isopropanol admixed with water,N-methylpyrrolidinone, toluene, and mixtures and combinations thereof.

The therapeutic substance or drug can be for inhibiting the activity ofvascular smooth muscle cells. More specifically, the active agent can beaimed at inhibiting abnormal or inappropriate migration and/orproliferation of smooth muscle cells for the inhibition of restenosis.The active agent can also include any substance capable of exerting atherapeutic or prophylactic effect in the practice of the presentinvention. For example, the agent can be for enhancing wound healing ina vascular site or improving the structural and elastic properties ofthe vascular site. Examples of agents include antiproliferativesubstances such as actinomycin D, or derivatives and analogs thereof(manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee,Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin Dinclude dactinomycin, actinomycin IV, actinomycin I₁, actinomycin X₁,and actinomycin C₁. The active agent can also fall under the genus ofantineoplastic, antiinflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel (e.g. TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g. Taxotere®, from Aventis S.A.,Frankfurt, Germany) methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrin, and antithrombins includesodium heparin, low molecular weight heparins, heparinoids, hirudin,argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck & Co.,Inc., Whitehouse Station, N.J.); calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand nameMevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonalantibodies (such as those specific for Platelet-Derived Growth Factor(PDGF) receptors), nitroprusside, phosphodiesterase inhibitors,prostaglandin inhibitors, suramin, serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. An example of an antiallergic agent is permirolastpotassium. Other therapeutic substances or agents which may beappropriate include alpha-interferon, genetically engineered epithelialcells, dexamethasone, and rapamycin.

FIG. 7 is a diagram illustrating the coating/drying chamber 600 holdingthe cartridge 500 with the coating applicator 740 positioned adjacentthereto. The coating applicator 740 includes a nozzle 710, reservoir 730and tubing 720 that places the nozzle 710 in fluid communication withthe reservoir 730. The coating applicator 740 is communicatively coupledto controlling electronics 400, which controls movement of the coatingapplicator 740 as well as dispensation of a coating substance, stored inthe reservoir 730, via nozzle 710 onto a stent in the spray chamber 670.During a spray coating process, the coating applicator 740 can move backand forth along the length of the stent to spray the stent. In addition,the stent mandrel 520 holding the stent also rotates during the spraycoating process to ensure that the stent is equally coated with thecoating substance.

After spraying, the controlling electronics 400 causes the cartridge 500to rotate in a counter clockwise direction such that one of the knobs530 pushes open gate 640 b so that the coated stent can enter the dryingportion of coating/drying chamber 600. The cartridge 500 can make a full360-degree revolution so that the stent can go through a subsequentspray coating process, thereby enabling multiple layers of a coatingsubstance or multiple layers of a plurality of different coatingsubstances to be formed on a stent.

In an embodiment of the invention, the coating/drying chamber 600includes a plurality of spray chambers 670 and coating applicators 740so that a plurality of different coating substances can be dispensedonto a stent during a coating/drying cycle.

In an example coating/drying process, the dryer 130 supplies heated airhaving a temperature of, for example, 50 to 80 degrees celsius. Theheated air can circulate within the drying section of the coating/dryingchamber 600 at a speed of up to about 20 meters/second. The cartridge500 makes 20 to 60 revolutions per process, leading to 20 to 60 coatinglayers applied to each stent mounted on the stent mandrels 520. Thecoating applicator can spray a stent mounted on the stent mandrel 520for about five to ten seconds at a rate of about 50 cubic millimetersper minute. The nozzle 710 can use about 15 psi atomization air pressureto atomize the composition dispensed from the nozzle 710.

Accordingly, the multiple stent coater/dryer apparatus 100 enableselimination of a long final oven bake of the stents because the solventis removed after application of each thin layer. Further, the multiplestent coater/dryer apparatus 100 minimizes drug-solvent interactionbecause the solvent is removed from each layer immediately after thecomposition is applied. In addition, the multiple stent coater/dryerapparatus 100 enables minimization of extraction of the drug in a lowerlayer into an upper layer because the solvent is removed immediately foreach layer after coating. Another benefit is that the multiple stentcoater/dryer apparatus 100 enables minimal handling between applicationsof layers. For example, the stents do not need to be weighed betweenapplications of layers. An additional benefit is that the multiple stentcoater/dryer apparatus 100 enables deposition of a higher coating weightper layer/coating cycle by drying off substantially all of the solventafter each spray coating cycle. Finally, the multiple stent coater/dryerapparatus 100 enables preheating of each stent prior to each cycle forbetter wetting.

The foregoing description of the illustrated embodiments of the presentinvention is by way of example only, and other variations andmodifications of the above-described embodiments and methods arepossible in light of the foregoing teaching. Components of thisinvention may be implemented using a programmed general purpose digitalcomputer, using application specific integrated circuits, or using anetwork of interconnected conventional components and circuits.Connections may be wired, wireless, modem, etc. The embodimentsdescribed herein are not intended to be exhaustive or limiting. Thepresent invention is limited only by the following claims.

1. A cartridge, comprising: a core; a plurality of stent mandrelsextending outwards from a circumference of the core, each stent mandrelcapable of supporting a stent; a first clutch coupled to the core andcapable of being removeably coupled to a first shaft such that rotationof the first shaft enables rotation of the core; and a second clutchcoupled to the plurality of stent mandrels and capable of beingremoveably coupled to a second shaft such that rotation of the secondshaft enables rotation of the stent mandrels.
 2. The cartridge of claim1, wherein the plurality of stent mandrels includes at least twelvestent mandrels.
 3. The cartridge of claim 1, wherein the plurality ofstent mandrels are evenly distributed along the circumference of thecore.